细胞因子/趋化因子在单纯疱疹病毒脑炎小鼠表达及生物信息学分析

目的 探讨单纯疱疹病毒脑炎(herpes simplex encephalitis,HSE)中细胞因子/趋化因子谱的表达情况,确定差异表达的因子及其相关的生物信息学作用.方法 单纯疱疹病毒1型(HSV-1)接种于Vero细胞,Reed-Muench法测定病毒滴度;实验组小鼠鼻腔接种HSV-1,建立动物感染模型,观察至接...

Expression profiles of cytokines/chemokines and bioinformatic analysis of the proteins with differential expression in the mice with herpes simplex virus encephalitis

Objective To explore the differently expressed cytokines and chemokines and analyze the associated bioinformatic characteristics of the selected factors to understand the pathways that lead to herpes simplex encephalitis (HSE). Methods Vero cells were used for the titer determination of herpes simplex virus type 1 (HSV-1) by Reed-Muench method. Mice in the experimental group were inoculated intranasally with HSV-1 to establish the virus infected animal models and observed to the 7^th day after inoculation. The mice were killed and the brain tissues were removed to prepare the paraffin sections with left cerebral hemisphere for pathological examination and brain tissue homogenate with right cerebral hemisphere for the cytopathic effects and cytokine chip assay. GO, KEGG, and PPIs analyses were employed to investigate the biological process (BP), pathways and interaction network of the differently expressed proteins (DEPs) in HSE mice. Results All of the animals suffered from HSE (100％) and three out of 15 mice died (20％) in the experimental group. However, all of the mice in control group were normal. Interestingly, there were no significant differences of the mortality and morbidity between the experimental group and the control (P>0.05). Virus-infected brain tissues showed inflammatory damages such as edema, hemorrhagic lesions, and immune cell infiltration. Conversely, no lesions were found in the control. A large number Vero cells were abscission and fusion after inoculated by the brain homogenate separated from the experimental group mice, no changes were found in control group. The virus gene of UL36 was detected by PCR only in the homogenate in the experimental mice brain. Seven DEPs and various proteins-related signal pathways were identified in HSE mice. Multiple biological processes which mainly implicated in immune cell activation and chemotaxis were screened by GO analysis; seven signal paths were selected by KEGG, such as TNF signal pathway and NOD signal pathway, et al. The DEPs constituted a pivotal protein interaction network by PPI, and IL-6, IL-1, IFN-γ and TNF-α were the main factors in the network. Conclusion Seven DEPs and a series of related signal pathways are selected, which might associate with the pathophysiological mechanisms responsible for HSE.